Morning ReportJuly 6, 2012

In the ER…

18 month old male with bruising and a bloody nose

History

ROS: Fell off chair 3 days ago, now mother noticing increasing size of bruise with no other known trauma, +bruising, +epistaxis, +small spots on entire body when woke up this morning URI ~1 week ago now resolved No fevers, no night sweats, no weight loss, no n/v/d, normal

appetite and activity level, no gross hematuria

PMHx: Full term, no complications. Not circumcised. Immunizations UTD – received 12 mo vaccines ~6 months. No medications. No history of eczema.

Social Hx: LAHW mother, father, older sister, 1 cat.

Family Hx: No bleeding disorders

Physical Exam Temp 37.0 HR 115 RR 18 O2 sat 99% on RA BP 87/46 Gen: Well-appearing, well nourished, no distress. Running around

the room HEENT: Anicteric sclera. Scattered bruises throughout the scalp. No

rhinorrhea or congestion. Dried blood in right nare. MMM. Petechiae on OP and palate. Blood blister on upper lip mucosa. Scattered petechiae around mouth

CV: RRR, no murmurs, 2+ pulses throughout Resp: CTAB/L, no wheezing, no rhonchi Abd: Soft, NT, normoactive BS. No distension, no masses. No HSM. MSK: Normal ROM LAD: Shotty anterior and posterior cervical adenopathy, all <1 cm Neuro: No focal deficits Skin: Petechiae, purpura throughout extremities, torso and abdomen.

No jaundice or pallor

One liner

18 mo M with no significant PMH presenting with sudden onset bruising and petechiae

Work-up

“Lab is calling to report a critical lab…”

Platelets 5

Platelets

Live 7-10 days

Thrombocytopenia <150K No symptoms >100K Minimal symptoms 50-100K Mild (cutaneous) symptoms 20-50K Moderate (cutaneous + mucosal)

symptoms 5-20K Severe symptoms (mucosal + CNS)

<5K

Thrombocytopenia

Increased destruction

Decreased production

Name that syndrome!thrombocytopenia

Kasabach-Merritt syndrome

Sequestration of platelets and coagulation activation in large vascular malformations

Fanconi anemia

Fanconi anemia ≠ Fanconi syndrome!

Autosomal recessive

Hypopigmented macules, café-au-lait macules

Abnormalities of thumbs

Microcephaly

Urogenital abnormalities

Short stature

Wiskott-Aldrich syndrome

X-linked recessive

Abnormal gene on proximal arm of X chromosome

Atopic dermatitis

Thrombocytopenic purpura

Increased susceptibility to infections

Thrombocytopenia-absent radii syndrome (TAR)

?defect of megakaryocyte Normal erythroid and myeloid

maturation

Bilateral absent radii

Normal thumbs

Skeletal, GU, heart anomalies

Bernard-Soulier syndrome

Autosomal recessive

Dysfunction/absence of platelet receptor for von Willebrand factor

Prolonged bleeding time

Easy bruising, severe hemorrhage with trauma/surgery

Increased destruction

Disseminated intravascular coagulation (DIC)

Hemolytic-uremic syndrome (HUS)

Thrombotic thrombocytopenic purpura (TTP)

Kasabach-Merritt syndrome

Immune thrombocytopenic purpura (ITP)

Drug induced

Mechanical platelet destruction

Platelet sequestration

Decreased production

Bone marrow failure or infiltrate Acquired aplastic anemia

Leukemia, infectious granuloma

Fanconi anemia

Infection

Nutritional

Thrombocytopenia and absent radii (TAR)

Wiskott-Aldrich syndrome

Bernard-Soulier syndrome

Cyanotic congenital heart disease

Back to our patient…

CBC 9.9>12.6/37.1<5, Smear: no schistocytes, +megakaryocytes

Type and Screen O+, Antibody negative, Coombs negative

ANA: pending

Autoplatelet antibody: pending

PT 12.6 PTT 27.5 INR 1.0

BMP normal

LDH normal

U/A 5-10 RBC, no WBC, no casts, no bacteria

CRP <3

Immune Thrombocytopenic Purpura

Isolated thrombocytopenia

Immune mediated destruction of normal platelets

Epidemiology

½ of cases occur in pediatric patients 2-10 year olds, peak 2-5 year olds

Most common cause of isolated thrombocytopenia in otherwise well children

60% of cases occur within 1 month of an infection

Seen following MMR vaccine

Clinical manifestations

Cutaneous bleeding

Mucosal bleeding

Absence of other symptoms

Guidelines

Diagnosis

History, physical, CBC, smear

Consider bone marrow biopsy if: Fever Bone/joint pain +family history HIV risk factors Skeletal or soft tissue morphologic abnormalities non-petechial rash Lymphadenopathy Abnormal Hgb, WBC, white cell morphology

To Treat or Not to Treat

Children with no or mild bleeding (skin manifestations only) be managed with observation* alone regardless of platelet count

Essential components: anticipatory guidance, follow-up, reliable parents

All patients: restrict activity (no contact sports), avoid medications with antiplatelet or anticoagulant activity

*can be done as an outpatient

Treat…

Any child with significant bleeding (mucosal bleeding) regardless of platelet count

Children with platelet count < 10K and cutaneous bleeding

Choices: IVIG Anti-D immunoglobulin Steroids

IVIG

IVIG can be used if a more rapid increase in the platelet count is desired

Meta-analysis comparing IVIG to steroids Primary outcome: platelets > 25K Steroids 26% less likely to achieve outcome

IVIG

Prevention of reticuloendothelial uptake of autoantibody-coated platelets

IVIG

Interaction of the autoantibodies with anti-idiotype antibodies in the IVIG

Giving IVIG

Single dose, 0.8-1 g/kg

Side effects Fever Nausea, vomiting Headache Aseptic meningitis Anaphylaxis Renal failure

Live vaccines must wait

Rhogam

Hgb >10, Rho(D) positive

Side effects: fever, chills, hemolytic anemia

Steroids

Reduce antibody production

Reduce reticuloendothelial system phagocytosis of antibody-coated platelets

Improve vascular integrity

Improve platelet production

Prognosis

20% go on to have chronic ITP (> 6-12 months)

Intracranial hemorrhage is rare – incidence of 0.1-0.5%

Compare

5 yo M with ALL s/p chemotherapy with a platelet count of 5K

5 yo M with ITP with a platelet count of 5K

PREP 2007

In examining a 4-year-old girl who is new to your practice, you discover that she has rudimentary thumbs and is well below the 5th percentile for both weight and height. You also observe irregular hyperpigmentation on the trunk and anogenital areas.

Of the following, the MOST likely hematologic disorder associated with these findings is:

A. Acute lymphoblastic leukemia

B. Bloom syndrome

C. Diamond-Blackfan anemia

D. Fanconi anemia

E. Thrombocytopenia and absent radii (TAR) syndrome

PREP 2005

An otherwise well 4-year-old boy is brought to your office because his mother has noticed bruising over the past 2 weeks. On physical examination he appears well and has no hepatosplenomegaly or adenopathy. There are scattered petechiae on the right upper arm, resolving bruises on the legs, and no evidence of new bruises. A complete blood count shows a platelet count of 50 x 103/mcL. The white blood cell and differential counts, hemoglobin, and hematocrit are normal

Of the following, the BEST next step in the management of this patient is to recommend:

A. administration of intravenous immunoglobulin therapy

B. administration of oral corticosteroid therapy

C. avoidance of sulfonamides

D. hospitalization for observation

E. performance of a bone marrow examination

Goals and Objectives

Review the differential diagnosis for thrombocytopenia and syndromes associated with thrombocytopenia

Review the pathophysiology of ITP

Review the current approach to diagnosis and management of ITP

References

http://www.uptodate.com/contents/treatment-and-prognosis-of-immune-idiopathic-thrombocytopenic-purpura-in-children?source=search_result&selectedTitle=3%7E150

http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-immune-idiopathic-thrombocytopenic-purpura-in-children?source=search_result&selectedTitle=4%7E150

Beck CE, Nathan PC, Parkin PC, Blanchette VS, Macarthur C. Corticosteroids versus intravenous immune globulin for the treatment of acute immune thrombocytopenic purpura in c hildren: a systematic review and meta-analysis of randomized-controlled trials. J Pediatr. 2005; 147 (4):521-527.

Buchanan GR. Thrombocytopenia during childhood: what the pediatrician needs to know. Peds in Review. Nov 2005; 401-409.

Consolini DM. Thrombocytopenia in infants and childrewn. Peds in Review. April 2011; 135-151.

Nuenert C, Lim C. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood (2011) 117: 4190-4207